|Year : 2014 | Volume
| Issue : 3 | Page : 134-138
Platelet indices: consideration in thrombocytopenia
DA Elsewefy, BA Farweez MD , RR Ibrahim
Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Egypt
|Date of Submission||15-Oct-2014|
|Date of Acceptance||03-Nov-2014|
|Date of Web Publication||31-Dec-2014|
Dr. B A Farweez
Clinical Pathology Department, Faculty of Medicine, Ain Shams University, 13 Ismail Ghanem street, Nozha Gadeda district, Heliopolis, Cairo 11769
Source of Support: None, Conflict of Interest: None
Background There is increasing evidence that platelet indices, such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR), have a significant role in the discrimination between hyperdestructive thrombocytopenia and hypoproductive thrombocytopenia, and they can be of great help as they are routinely generated by automated cell counters.
Objective In this study, we aimed to assess the sensitivity and specificity of these indices and set cutoff values that aid in the diagnosis of thrombocytopenia cause.
Materials and methods We recruited 20 individuals as the control group and 80 thrombocytopenic patients, who were divided into two groups: group I ( n = 40) included newly diagnosed immune thrombocytopenic purpura (ITP) patients (hyperdestructive thrombocytopenia), whereas group II ( n = 40) included hypoproductive thrombocytopenia patients. The MPV and platelet distribution width were derived from automated cell counter results. The P-LCR was calculated.
Results In ITP (hyperdestructive thrombocytopenia) patients, the MPV and P-LCR were significantly higher; the best cutoff value for MPV was greater than 9.7 fl and for P-LCR was greater than 33.6%, with a diagnostic accuracy of 70.1 and 99.6%, respectively.
Conclusion The MPV and P-LCR provide information about the underlying conditions of thrombocytopenia. These indices should be considered in the diagnosis of thrombocytopenia. The P-LCR can be safely relied upon for a positive diagnosis of ITP.
Keywords: hyperdestructive thrombocytopenia; hypoproductive thrombocytopenia; immune thrombocytopenic purpura; mean platelet volume; platelet distribution width; platelet large cell ratio
|How to cite this article:|
Elsewefy D A, Farweez B A, Ibrahim R R. Platelet indices: consideration in thrombocytopenia. Egypt J Haematol 2014;39:134-8
| Introduction|| |
Platelet counts below normal values define thrombocytopenia but do not reveal the underlying pathomechanism  . Advances in automated blood cell analyzers have made it possible to measure various parameters. Platelet indices, such as mean platelet volume (MPV), platelet distribution width (PDW), and platelet large cell ratio (P-LCR), may provide some important information  . Thus, we aim to investigate their usefulness in discriminating between immune thrombocytopenic purpura (ITP; hyperdestructive thrombocytopenia) and hypoproductive thrombocytopenia, to assess their sensitivity and specificity, and to obtain cutoff values in an attempt to consider the use of these indices in the initial evaluation of these patients.
| Patients and methods|| |
The present study included 80 thrombocytopenic patients divided into two groups [40 patients with newly diagnosed ITP (group I) and 40 patients with hypoproductive thrombocytopenia (group II)] and 20 age-matched and sex-matched healthy individuals as the control group.
A diagnosis of ITP (group I) was made according to the recommendations of the 'International Consensus Report on the Investigation and Management of Primary Immune Thrombocytopenia'  . It was established on the basis of proper history taking, with special attention to a history of intake of medications known to cause thrombocytopenia or associated viral infections; a bone marrow aspirate showing normal marrow with increased or adequate megakaryocytes showing defective platelet budding and separation; and disease duration less than 3 months. Patients were subjected to thorough clinical examination especially for the presence of purpuric eruptions or ecchymotic patches and their distribution, as well as for splenomegaly, hepatomegaly, and lymphadenopathy. Laboratory investigations were performed to exclude signs of concomitant autoimmune disorders such as juvenile rheumatoid arthritis, systemic lupus erythematosis, vitiligo, and type 1 diabetes mellitus. Ten ITP patients had not received corticosteroids or any other medication, and the remaining 30 patients had received treatment including corticosteroids. Exclusion criteria were a recent manifestation of active infection, or secondary causes of ITP such as systemic lupus erythematosis.
The hypoproductive thrombocytopenia group (group II) included patients with acute leukemia, whose diagnosis was based on bone marrow examination, and cytochemical and immunophenotyping criteria, patients with idiopathic aplastic anemia defined by pancytopenia and aplasia on bone marrow examination, with exclusion of thrombasthenia and collagen vascular disorders, patients with myelodysplastic syndrome, in whom diagnosis was based on bone marrow examination and cytogenetic studies, and patients under chemotherapy.
Laboratory assessments for the patient and the control groups included the following:
- Assessment of complete blood count, MPV, and PDW on Beckman Coulter LH 750 (Beckman Coulter, Miami, Florida, USA). Calibration was assessed daily with the commercial calibrant 5C (Beckman Coulter). All whole-blood counts were assayed within 2 h of sample collection. The P-LCR was estimated by the MedCalc for Windows, version 12.5 (MedCalc Software, Ostend, Belgium) program from platelet histograms as the percentage of platelets with a size of more than 12 fl.
- Microscopic examination of a peripheral blood film stained with Leishman stain.
The study design was approved by the Scientific Research Committee and is in accordance with the Declaration of Helsinki 1975. All parents and/or surrogates were informed about the aims of the study. Formal written consent was obtained from the participants themselves or from their caregivers who agreed to their participation in the study.
Patient data were tabulated and processed using SPSS (17.0; SPSS Inc., Chicago, Illinois, USA) for Windows XP. Quantitative variables were expressed as mean, SD, and range and analyzed using Student's unpaired t-test. Qualitative data were expressed as frequency and percentage and were analyzed using the χ2 -test. Correlation analysis was carried out using the linear correlation coefficient and the ANOVA test to assess the strength of association between two variables.
A P-value less than 0.05 was considered statistically significant. A receiver-operating characteristic curve was constructed to establish the clinically relevant cutoff values for the studied parameters, with calculation of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy.
| Results|| |
Data are presented in [Table 1], [Table 2], [Table 3], [Table 4], [Table 5] and [Figure 1].
|Table 1 Comparison of platelet count and platelet indices between group I and group II|
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|Table 2 Comparison of platelet count and platelet indices between group I and the control group|
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|Table 3 Comparison of platelet count and platelet indices between group II and the control group|
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|Table 4 Correlation studies between platelet indices and platelet count in groups I and II|
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|Table 5 Diagnostic performance of MPV and P-LCR as diagnostic markers of ITP|
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|Figure 1 ROC curve for P-LCR to determine the best cut off to differentiate between ITP and hypoproductive thrombocytopenia patients. A Cut off value for P-LCR >33.6% yielded 99.6% accuracy as a diagnostic marker for ITP.|
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This study included 80 patients with thrombocytopenia, who were classified as follows:
Group I included 40 patients with newly diagnosed idiopathic ITP. These included 16 male and 24 female patients, with a male : female ratio of 1 : 1.5. Their ages ranged from 8 to 49 years, with a mean age of 34.1 ± 10.4 years.
Group II included 40 patients with hypoproductive thrombocytopenia due to different causes. These included 10 patients with aplastic anemia, 17 patients with acute leukemia, three patients with myelodyplasia, and 10 patients under treatment with chemotherapy. There were 16 male and 24 female patients, with a male : female ratio of 1 : 1.5. Their ages ranged from 24 to 67 years, with a mean age of 50.4 ± 9.50 years.
Twenty healthy age-matched and sex-matched individuals were selected for comparison as the control group.
Platelet counts and platelet indices were compared between groups I and II (as shown in [Table 1]), as well as between each of the patient groups and the control group ([Table 2] and [Table 3]). Platelet counts and PDW did not show significant differences between the two patient groups, whereas MPV and P-LCR were significantly higher in group I compared with group II (P = 0.008, P < 0.001 respectively).
On comparison of the two patient groups with the control group, the P-LCR was found to be significantly higher in group I (P < 0.001) and significantly lower in group II (P = 0.035), whereas PDW and MPV did not show a significant difference in the two patient groups.
In patients with ITP, significant positive correlations between MPV and PDW (r = 0.312, P = 0.048), PDW and P-LCR (r = 0.405, P = 0.010), and MPV and P-LCR were found (r = 0.561, P < 0.010). In addition, significant positive correlations were found between MPV and PDW (r = 0.611, P < 0. 001), PDW and P-LCR (r = 0.373, P = 0.018), and MPV and P-LCR (r = 0.315, P < 0.047) in hypoproductive thrombocytopenia patients. However, no significant correlations between any of the platelet indices and the platelet counts were found in either ITP patients or hypoproductive thrombocytopenia patients. ([Table 4]).
Diagnostic performance characteristics of platelet indices
Diagnostic performance characteristics of platelet indices were determined by receiver-operating characteristic curve analysis.
A cutoff value greater than 9.7 fl for MPV yielded 70% diagnostic accuracy and a cutoff value greater than 33.6% for P-LCR yielded 99.6% diagnostic accuracy for the diagnosis of ITP ([Table 5]; [Figure 1]).
| Discussion|| |
The diagnosis and management of thrombocytopenia is a growing component in the practice of hematology. The frequency with which hematologists are called in for a consultation for thrombocytopenia continues to increase with the advent of routine automated platelet determinations  and, although platelet indices, such as MPV, PDW, and P-LCR, have been available for some time, their clinical usefulness has been elusive  .
Thrombocytopenia is a common clinical manifestation of many diseases and has numerous causes, including decreased bone marrow production, increased spleen sequestration, and accelerated destruction of platelets  . One of the major causes of increased platelet destruction is immune thrombocytopenia, in which autoantibodies bind to platelet antigens, causing their premature destruction by the reticularendothelial system, particularly the spleen  . Decreased bone marrow production due to hematological malignancy, tumor infiltration, aplastic anemia, and chemotherapy is another common cause of thrombocytopenia, and its diagnosis requires confirmation by hematological morphological examination, bone marrow examination, immunophenotyping, and karyotyping, which are familiar only to hematologists  .
The present study was conducted on 80 thrombocytopenic patients: 40 patients had ITP, designated as the hyperdestructive thrombocytopenia group, and 40 patients had hypoproductive thrombocytopenia (10 aplastic anemia patients, 17 acute leukemia patients, three myelodysplastic syndrome (MDS) patients, and 10 patients under chemotherapy), and 20 apparently normal individuals matched for age and sex constituted the control group.
Our study showed that MPV did not show a significant difference between either the ITP patients and the control group or the hypoproductive thrombocytopenia group and the control group. Similarly, Borkataky et al.  found no significant difference in the MPV between the destructive thrombocytopenia groups and the control group.
Meanwhile, ITP patients showed significantly higher MPV results than hypoproductive thrombocytopenic patients. A cutoff value for MPV greater than 9.7 fl was able to differentiate between ITP and hypoproductive thrombocytopenia patients with a diagnostic accuracy of 70%. Similarly, previous work by researchers such as Kaito et al.  , Ntaios et al.  , Xu et al.  , and Shah et al.  reported that MPV was higher in ITP patients compared with hypoproductive thrombocytopenic patients, which reflected an increase in the production rate, and they established cutoff values ranging from greater than 9 fl to greater than 11 fl.
Although Numbenjapon et al.  reported that MPV could be used in distinguishing hyperdestructive from hypoproductive thrombocytopenia, they proposed a cutoff value of 7.9 fl, which is lower than the previously reported cutoff values.
This variation in the cutoff values of MPV in different studies can be attributed to the difference in the selection of patients with hypoproductive thrombocytopenia (comparative group with ITP).
Another explanation for the differences in the cutoff values of MPV in different studies can be the difference in the type of the hematological analyzer used, as older automated analyzers, which could have been used in these studies, cannot discriminate platelets from other similarly sized particles such as fragmented red or white blood cells, cell debris, and immune complexes. Moreover, they do not count large or giant platelets because they cannot be differentiated from red blood cells. Furthermore, many papers in the literature have shown that MPV is dependent on a number of variables, including the time of analysis after venipuncture, the anticoagulant used, the specimen storage temperature, and counter technologies  .
In the present study, the P-LCR was significantly higher in ITP patients compared with the control group and significantly lower in hypoproductive thrombocytopenia patients compared with the control group. Likewise, Borkataky et al.  reported a significantly lower P-LCR in nonmegaloblastic hypoproliferative thrombocytopenia patients than in the control group, but they did not report a difference in the P-LCR between ITP patients and the control group. However, in our study the P-LCR was found to be significantly higher in ITP patients compared with hypoproductive thrombocytopenia patients, and a cutoff value greater than 33.6% yielded 100% diagnostic sensitivity for ITP. Therefore, it was effective in distinguishing ITP from hypoproductive thrombocytopenia. Similarly, Ntaios et al.  and Kaito et al.  reported nearly similar cutoff value of greater than 30%, with diagnostic sensitivities of 90.4 and 91.4%, respectively. In addition, Babu and Basu  and Borkataky et al.  reported that the P-LCR was increased in destructive thrombocytopenia patients compared with hypoproliferative thrombocytopenia and nonmegaloblastic hypoproliferative thrombocytopenia patients, although this increase was not statistically significant, and they concluded that the P-LCR can be a good aid in the differential diagnosis of conditions associated with abnormal platelet counts.
With regard to PDW, there was no significant difference between the two patient groups, nor between the patient groups and the control group in our study. In contrast, Shah et al. and Borkataky et al.  found that the PDW was higher in ITP patients compared with acute myeloid leukemia patients and nonmegaloblastic hypoproliferative patients, respectively. In addition, Kaito et al.  suggested a cutoff value of greater than 17 fl for PDW to distinguish ITP from hypoproductive thrombocytopenia, with 71.8% diagnostic sensitivity and 95% specificity. Similarly, Ntaios et al.  suggested a cutoff value between 15 and 17 fl, with 100% sensitivity, specificity, positive predictive value, and negative predictive value.
However, conflicting results were obtained by Xu et al.  when comparing PDW between ITP patients and patients with bone marrow failure (BMF), in whom higher PDW results were obtained compared with ITP patients, and they commented that this was consistent with a significant dysplasia of hematopoiesis in the bone marrow in BMF patients. Thus, as observed by Leader et al.  , the majority of the data on the diagnostic predictive efficiency of MPV and PDW in thrombocytopenic patients are from retrospective studies, some of which had small study populations and confounding factors influencing platelet volume. In addition, the cutoff values derived from these retrospective studies have not been validated prospectively.
Finally, the fact that platelet indices are increased in ITP has been recognized since 1983. However, this knowledge gained very limited use in the daily clinical practice. In our study, we concluded that increased MPV and P-LCR provide a reliable positive diagnosis of ITP in the case of thrombocytopenic patients, especially a high P-LCR. In the future, improved research designs and standardized measurements for platelet indices may significantly increase the diagnostic predictive power of platelet indices in the differential diagnosis of thrombocytopenia.
| Acknowledgements|| |
Conflicts of interest
There are no conflicts of interest.
| References|| |
Strauss G, Vollert C, von Stackelberg A, Weimann A, Gaedicke G, Schulze H. Immature platelet count: a simple parameter for distinguishing thrombocytopenia in pediatric acute lymphocytic. Pediatr Blood Cancer
Park Y, Schoene N, Harris W. Mean platelet volume as an indicator of platelet activation: methodological issues. Platelets
Provan D, Stasi R, Newland AC, Blanchette VS, Bolton-Maggs P, Bussel JB, et al.
International consensus report on the investigation and management of primary immune thrombocytopenia. Blood
Cines DB, Bussel JB, McMillan RB, Zehnder JL. Congenital and acquired thrombocytopenia. Hematology Am Soc Hematol Educ Program
Xu RL, Zheng ZJ, Ma YJ, Hu YP, Zhuang SH. Platelet volume indices have low diagnostic efficiency for predicting bone marrow failure in thrombocytopenic patients. Exp Ther Med
Handin RI. Bleeding and thrombosis. In: Harrison TS, Fauci AS, Braunwald E, Isselbacher KJ editors. Harrison's principles of internal medicine, 14th ed. New York: McGraw-Hill
; 1998. 8490.
Woods VLJr, Kurata Y, Montgomery RR, Tani P, Mason D, Oh EH, et al.
Autoantibodies against platelet glycoprotein Ib in patients with chronic immune thrombocytopenic purpura. Blood
Borkataky S, Jain R, Gupta R, Singh S, Krishan G, Gupta K, et al.
Role of platelet volume indices in the differential diagnosis of thrombocytopenia: a simple and inexpensive method. Hematology
Kaito K, Otsubo H, Usui N, Yoshida M, Tanno J, Kurihara E, et al.
Platelet size deviation width, platelet large cell ratio, and mean platelet volume have sufficient sensitivity and specificity in the diagnosis of immune thrombocytopenia. Br J Haematol
Ntaios G, Papadopoulos A, Chatzinikolaou A, Saouli Z, Karalazou P, Kaiafa G, et al.
Increased values of mean platelet volume and platelet size deviation width may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura. Acta Haematol
Shah AR, Chaudhari SN, Shah MH Role of platelet parameters in diagnosing various clinical conditions. Natl J Med Res
Numbenjapon T, Mahapo N, Pornvipavee R, Sriswasdi C, Mongkonsritragoon W, Leelasiri A, et al.
A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive thrombocytopenia. Int J Lab Hematol
Noris P, Klersy C, Gresele P, Giona F, Giordano P, Minuz P, on behalf of the Italian 'Gruppo di Studiodelle Piastrine Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: a multicentric, real life study. Br J Haematol
Babu E, Basu D. Platelet large cell ratio in the differential diagnosis of abnormal platelet counts. Indian J Pathol Microbiol
Leader A, Pereg D, Lishner M. Are platelet volume indices of clinical use? A multidisciplinary review. Ann Med
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]